Recent advances in the treatment and monitoring of HIV-1 infection have substantially diminished HIV-associated illness and mortality;however the management of HIV-infected patients has become increasingly complex. We are conducting studies that: (1) evaluate novel therapeutic strategies in the management of hepatitis C virus (HCV)-infected individuals, and (2) identify the signature host response characteristics that predict HCV response to existing treatment and aid in developing better future therapies. This past year, we were able to (1) determine the safety, tolerability and effectiveness of a novel regimen including twice monthly Albumin-Interferon alpha 2b along with Ribavirin to treat Hepatitis C in HIV co-infected subjects;(2) demonstrate the distinct influence of ongoing HIV replication on host immune activation profiles in Hepatitis C infected subjects;(3) demonstrate the effect of race and baseline immune status (CD4+ T cell count) on response rates to HCV using the pegylated Interferon-alpha and Ribavirin (4) demonstrate mechanism(s) that influence therapeutic responses to pegylated Interferon and ribavirin based therapy for HCV and (5) demonstrate the role individual Interferon-inducible gene products in controlling HCV replication in vitro.